Skip to main content
Article thumbnail
Location of Repository

Protein X of Borna Disease Virus Inhibits Apoptosis and Promotes Viral Persistence in the Central Nervous Systems of Newborn-Infected Rats ▿

By Marion Poenisch, Nils Burger, Peter Staeheli, Georg Bauer and Urs Schneider

Abstract

Borna disease virus (BDV) is a neurotropic member of the order Mononegavirales with noncytolytic replication and obligatory persistence in cultured cells and animals. Here we show that the accessory protein X of BDV represents the first mitochondrion-localized protein of an RNA virus that inhibits rather than promotes apoptosis induction. Rat C6 astroglioma cells persistently infected with wild-type BDV were significantly more resistant to death receptor-dependent and -independent apoptotic stimuli than uninfected cells or cells infected with a BDV mutant expressing reduced amounts of X. Confocal microscopy demonstrated that X colocalizes with mitochondria and expression of X from plasmid DNA rendered human 293T and mouse L929 cells resistant to apoptosis induction. A recombinant virus encoding a mutant X protein unable to associate with mitochondria (BDV-XA6A7) failed to block apoptosis in C6 cells. Furthermore, Lewis rats neonatally infected with BDV-XA6A7 developed severe neurological symptoms and died around day 30 postinfection, whereas all animals infected with wild-type BDV remained healthy and became persistently infected. TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling) staining revealed a significant increase in the number of apoptotic cells in the brain of BDV-XA6A7-infected animals, whereas the numbers of CD3+ T lymphocytes were comparable to those detected in animals infected with wild-type BDV. Our data thus indicate that inhibition of apoptosis by X promotes noncytolytic viral persistence and is required for the survival of cells in the central nervous system of BDV-infected animals

Topics: Cellular Response to Infection
Publisher: American Society for Microbiology (ASM)
OAI identifier: oai:pubmedcentral.nih.gov:2668499
Provided by: PubMed Central
Download PDF:
Sorry, we are unable to provide the full text but you may find it at the following location(s):
  • http://www.pubmedcentral.nih.g... (external link)
  • Suggested articles


    To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.